Pilot Study of Oral Probiotic Bacteria Supplementation to Reduce Chronic Immune Activation in HIV-infected Malian Women

NCT02448238 | Completed

• 2 other identifiers: HM15330VCUHIV001
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The composition of the intestinal bacterial flora effects gut immunologic function and intestinal barrier integrity. HIV infection impairs gut immune and epithelial function resulting in an altered gut bacterial flora and "leakage" of gut bacterial products into the bloodstream. These bacterial products can overstimulate the immune system leading to increased inflammation and HIV disease progression. The investigators will investigate whether oral supplementation of certain beneficial "probiotic" bacteria may attenuate these processes in HIV infected women in Mali, Africa. This is a single arm study to evaluate the effect of 12 weeks of combination oral probiotic supplementation (VSL#3, Sigma-Tau Pharmaceuticals - containing 9 × 1011 bacteria of 8 species: S. thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus paracasei, and Lactobacillus bulgaricus) on plasma biomarkers of immune cell activation, and inflammation. The study population will be 50 chronically HIV-infected but generally healthy, non-pregnant, Malian women subjects with CD4+ T-cell count ≥ 350 cells/mm3 who are not receiving antiretroviral therapy. Blood plasma/serum and fecal sampling will occur at baseline, 4, and 12 week as well as at 24 weeks. At these time points, probiotic will be dispensed, a medical history will be obtained, and adherence will be assessed. Prior to study entry, subjects will have eligibility and safety labs will be obtained and detailed baseline medical and symptom histories, demographics, weight, and stool frequency information will be recorded. A stress assessment questionnaire will be completed at baseline and week 12 to determine the effect of this intervention on stress levels. The primary study outcome is to assess change (baseline to 12 week) in plasma soluble CD14 (a marker of monocyte response to bacterial endotoxin which has been associated with mortality) with study probiotic. Other outcomes will include assessing change (baseline to 12 week) in plasma interleukin-6, soluble CD163 (another monocyte activation marker), d-dimer (a marker of coagulopathy), intestinal fatty acid binding protein (a marker of gut epithelial cell injury) and fecal calprotectin (a marker of gut inflammation), as well as CD4+ T-cell counts, self reported stool quality (using the Bristol Stool Scale), safety and tolerability of the VSL#3 probiotic, and level of stress.

Conditions

HIV

Keywords

Human Immunodeficiency Virus; probiotic; microbial translocation; immune activation; inflammation; VSL#3; Mali; Africa

Outcome Measures

Primary Outcomes (1)

• change in plasma soluble CD14 (sCD14)

  sCD14 is marker of monocyte response to endotoxin associated with mortality

  baseline to week 12

Secondary Outcomes (8)

• change in plasma soluble CD163 (sCD163)

  baseline to week 12

• change in plasma interleukin-6 (IL-6)

  baseline to week 12

• change in plasma d-dimer

  baseline to week 12

• change in plasma intestinal fatty acid biding protein

  baseline to week 12

• change in CD4+ T cell counts

  baseline to week 12

Study Arms (1)

probiotic

EXPERIMENTAL

This is a single arm study all subjects will receive the study VSL#3 probiotic. Subjects will take 1 sachet of powder orally daily for 12 weeks

Other: VSL#3® probiotic

Interventions

VSL#3® probiotic OTHER

Other: VSL#3® probiotic VSL#3® DS (Sigma-Tau Pharmaceuticals) is a well characterized water soluble, live (9 × 1011 bacteria/sachet), lyophilized preparation of 8 probiotic bacterium that have been detailed previously. Subjects will take 1 sachet of powder orally daily for 12 weeks. As many Malian homes lack refrigeration, subjects will be issued a special "canari", a commonly used earthenware water container also containing sand that works on the principal of "trans-evaporation" to keep contents at room temperature (\~24°C) even in warmer climates. We have verified this in country. Probiotics will be placed in a sealed plastic bag within a sealed jar in the sand of the canari. At the research site, probiotics will be kept refrigerated (4-8°C) in a study provided refrigerator

probiotic

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load.
• No plans to initiate ART during the course of the proposed study. NOTE: Subjects who meet WHO treatment guidelines for initiating ART once enrolled should begin therapy as clinically indicated. These subjects must stop study treatment, and will be followed on study/off study treatment.
• Screening CD4+ T-cell count ≥ 350 cells/mm3 performed in a laboratory that has a Malian National Institute for Public Health and Research (INRSP) certification, or its equivalent, within 45 days prior to study entry.
• Laboratory values obtained within 45 days prior to entry as follows:
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Hemoglobin ≥ 10.0 g/dL
• Platelet count ≥ 50,000/mm3
• Female subjects of reproductive potential \[defined as girls who have reached menarche or women who have not been post-menopausal for at least 12 consecutive months, i.e., who have had menses within the preceding 12 months, or have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation)\] must have a negative serum or urine pregnancy test performed within 45 days prior to entry.
• Female subjects participating in sexual activity that could lead to pregnancy must agree to use at least one of the following forms of birth control for at least 45 days prior to study entry until the final study visit:
• Condoms (male or female) with or without a spermicidal agent
• Diaphragm or cervical cap with spermicide
• Intrauterine device (IUD)
• Hormone-based contraceptive (pill, injection, implants)
• Female subjects who are not of reproductive potential are eligible without requiring the use of a contraceptive. Acceptable documentation of sterilization, other contraception methods, menopause and reproductive potential is patient-reported history at any time prior to or during screening.
• Malian women age =\> 18 years.

You may not qualify if:

• Pregnant.
• Use of any antiretroviral agent during or within 24 weeks prior to study entry.
• Use of any of the following medications for more than 3 consecutive days during or within 45 days prior to study entry:
• Immunosuppressives
• Immune modulators
• Antineoplastic/Anticancer agents
• Probiotics
• Anticoagulants ( Aspirin is permitted )
• Active illicit drug or alcohol use or dependence, or conditions that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Anticipated antibiotic use during the study or use within 45 days prior to study entry. Topical antibiotics are permitted.
• Known cirrhosis or severe liver disease (e.g., ascites, encephalopathy, history of variceal bleeding).
• Recent (within 12 weeks) history of, or active, bowel obstruction, inflammatory bowel disease, colitis, intestinal bleeding, GI malignancy, or severe GI motility disorders including severe constipation or severe diarrhea (\>5 stools day/average) or severe swallowing disorders.
• Active gastrointestinal parasitic infection.
• Major GI tract surgery within 45 days prior to study entry.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Nianankoro Fomba Hospital

Ségou, Ségou, BP169, Mali

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Inflammation

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel E Nixon, DO, PhD

  Virginia Commonwealth University, USA

  PRINCIPAL INVESTIGATOR

• Saba Masho, MD, MPH

  Virginia Commonwealth University, USA

  STUDY DIRECTOR

• Susan Kornstein, MD

  Virginia Commonwealth University, USA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2015
• First Posted: May 19, 2015
• Study Start: May 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: June 14, 2017

Record last verified: 2017-06

Locations

MA (1)